Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarisations and fibrillation (original) (raw)

Kettlewell, Sarah, Burton, Francis L., Smith, Godfrey L. ORCID: https://orcid.org/0000-0003-4821-9741 and Workman, Antony J. ORCID: https://orcid.org/0000-0002-5429-8303(2013) Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarisations and fibrillation.Cardiovascular Research, 99(1), pp. 215-224. (doi: 10.1093/cvr/cvt087) (PMID:23568957) (PMCID:PMC3687753)

Abstract

Aims: Atrial fibrillation (AF) is increased in patients with heart failure resulting from myocardial infarction (MI). We aimed to determine the effects of chronic ventricular MI in rabbits on the susceptibility to AF, and underlying atrial electrophysiological and Ca2+-handling mechanisms. Methods and results: In Langendorff-perfused rabbit hearts, under beta-adrenergic-stimulation with isoproterenol (1 µM; ISO), 8 weeks MI decreased AF threshold, indicating increased AF-susceptibility. This was associated with increased atrial action potential duration-alternans at 90% repolarisation, by 147%, and no significant change in mean APD or atrial global conduction velocity (n=6-13 non-MI hearts, 5-12 MI). In atrial isolated myocytes, also under beta-stimulation, L-type Ca2+ current (ICaL) density and intracellular Ca2+-transient amplitude were decreased by MI, by 35% and 41%, respectively, and the frequency of spontaneous depolarisations (SDs) was substantially increased. MI increased atrial myocyte size and capacity, and markedly decreased transverse-tubule density. In non-MI hearts perfused with ISO, the ICaL-blocker nifedipine, at a concentration (0.02 µM) causing an equivalent ICaL-reduction (35%) to that from the MI, did not affect AF-susceptibility, and decreased APD. Conclusion: chronic MI in rabbits remodels atrial structure, electrophysiology and intracellular Ca2+-handling. Increased susceptibility to AF by MI, under beta-adrenergic-stimulation, may result from associated production of atrial APD-alternans and SDs, since steady-state APD and global conduction velocity were unchanged under these conditions, and may be unrelated to the associated reduction in whole-cell ICaL. Future studies may clarify potential contributions of local conduction changes, and cellular and sub-cellular mechanisms of alternans, to the increased AF-susceptibility.

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Funder and Project Information

1

Atrial remodelling of calcium handling and electrophysiology in heart failure.

Antony Workman

PG/09/028/27149

RI CARDIOVASCULAR & MEDICAL SCIENCES

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